BACKGROUND Gestational diabetes mellitus(GDM)is associated with a heightened level of oxidative stress,which is characterized by the overproduction of reactive oxygen species(ROS)from mitochondria.Previous studies sho...BACKGROUND Gestational diabetes mellitus(GDM)is associated with a heightened level of oxidative stress,which is characterized by the overproduction of reactive oxygen species(ROS)from mitochondria.Previous studies showed that mitochondrial dysfunction is regulated by dynamin-related protein 1(Drp1)and p66Shc in GDM.AIM The aim was to investigate the expression of Drp1 and p66Shc and their possible mechanisms in the pathogenesis of GDM.METHODS A total of 30 pregnant women,15 with GDM and 15 without GDM,were enrolled.Peripheral blood mononuclear cells and placental tissue were collected.The human JEG3 trophoblast cell line was cultivated in 5.5 mmol/L or 30 mmol/L glucose and transfected with wild-type(wt)-p66Shc and p66Shc siRNA.P66Shc and Drp1 mRNA levels were detected by quantitative real-time polymerase chain reaction.The expression of p66Shc and Drp1 was assayed by immunohistochemistry and western blotting.ROS was assayed by dihydroethidium staining.RESULTS The p66Shc mRNA level was increased in the serum(P<0.01)and placentas(P<0.01)of women with GDM,and the expression of Drp1 mRNA and protein were also increased in placentas(P<0.05).In JEG3 cells treated with 30 mmol/L glucose,the mRNA and protein expression of p66Shc and Drp1 were increased at 24 h(both P<0.05),48 h(both P<0.01)and 72 h(both P<0.001).ROS expression was also increased.High levels of Drp1 and ROS expression were detected in JEG3 cells transfected with wt-p66Shc(P<0.01),and low levels were detected in JEG3 cells transfected with p66Shc siRNA(P<0.05).CONCLUSION The upregulated expression of Drp1 and p66shc may contribute to the occurrence and development of GDM.Regulation of the mitochondrial fusion-fission balance could be a novel strategy for GDM treatment.展开更多
Introduction:Letrozole showed higher ovulation and live birth rates than clomiphene in infertile women with polycystic ovary syndrome(PCOS).Berberine,a major active component of Chinese herbal medicine rhizomacoptidis...Introduction:Letrozole showed higher ovulation and live birth rates than clomiphene in infertile women with polycystic ovary syndrome(PCOS).Berberine,a major active component of Chinese herbal medicine rhizomacoptidis,has been used to improve insulin resistance to facilitate ovulation induction in women with PCOS,but there is no study reporting the live birth or its potential as a complementary treatment to letrozole.We aim to determine the efficacy of letrozole with or without berberine in achieving live births among 644 infertile women with PCOS in China's Mainland.Methods and analysis:This is a prospective,randomized,multicentre,double-blinded,controlled design.Infertile women with PCOS were randomized into three-arm,letrozole and berberine,letrozole and berberine placebo,letrozole placebo and berberine.Data and blood were collected at baseline,the third month and sixth month after treatment,or immediately were collected if subject was pregnant.Statisticians and clinical investigators were blinded to treatment allocation and treatment related study results until the central database was locked for final data extraction and analysis determined.The statistical analysis plan described basic analysis principles,methods commonly encountered in data analysis issues,and the specific statistical procedures for analyzing the primary,secondary,and safety outcomes.Ethics and dissemination:The study was approved by the ethics committee of the First Affiliated Hospital,Heilongjiang University of Chinese Medicine.The study findings will be disseminated through peer-reviewed publications and conference presentations.Trial registration:Chinese Clinical Trial Registry:Chi CTR-TRC-09000376.Clinical Trials.gov identifier:NCT01116167.展开更多
基金The Scientific Research Fund of Qilu Hospital(Qingdao),No.QDKY2015ZD04.
文摘BACKGROUND Gestational diabetes mellitus(GDM)is associated with a heightened level of oxidative stress,which is characterized by the overproduction of reactive oxygen species(ROS)from mitochondria.Previous studies showed that mitochondrial dysfunction is regulated by dynamin-related protein 1(Drp1)and p66Shc in GDM.AIM The aim was to investigate the expression of Drp1 and p66Shc and their possible mechanisms in the pathogenesis of GDM.METHODS A total of 30 pregnant women,15 with GDM and 15 without GDM,were enrolled.Peripheral blood mononuclear cells and placental tissue were collected.The human JEG3 trophoblast cell line was cultivated in 5.5 mmol/L or 30 mmol/L glucose and transfected with wild-type(wt)-p66Shc and p66Shc siRNA.P66Shc and Drp1 mRNA levels were detected by quantitative real-time polymerase chain reaction.The expression of p66Shc and Drp1 was assayed by immunohistochemistry and western blotting.ROS was assayed by dihydroethidium staining.RESULTS The p66Shc mRNA level was increased in the serum(P<0.01)and placentas(P<0.01)of women with GDM,and the expression of Drp1 mRNA and protein were also increased in placentas(P<0.05).In JEG3 cells treated with 30 mmol/L glucose,the mRNA and protein expression of p66Shc and Drp1 were increased at 24 h(both P<0.05),48 h(both P<0.01)and 72 h(both P<0.001).ROS expression was also increased.High levels of Drp1 and ROS expression were detected in JEG3 cells transfected with wt-p66Shc(P<0.01),and low levels were detected in JEG3 cells transfected with p66Shc siRNA(P<0.05).CONCLUSION The upregulated expression of Drp1 and p66shc may contribute to the occurrence and development of GDM.Regulation of the mitochondrial fusion-fission balance could be a novel strategy for GDM treatment.
基金Funded by the National Public Welfare Projects for Chinese Medicine(200807021)of Chinathe "11th–Five" Supportive Program for Science and Technology of China(2007BAI20B015)+1 种基金the Heilongjiang Province Foundation for Outstanding Youths(JC200804)the Intervention for Polycystic Ovary Syndrome Based on Traditional Chinese Medicine Theory-‘Tian Gui Shi Xu’(2011TD006)
文摘Introduction:Letrozole showed higher ovulation and live birth rates than clomiphene in infertile women with polycystic ovary syndrome(PCOS).Berberine,a major active component of Chinese herbal medicine rhizomacoptidis,has been used to improve insulin resistance to facilitate ovulation induction in women with PCOS,but there is no study reporting the live birth or its potential as a complementary treatment to letrozole.We aim to determine the efficacy of letrozole with or without berberine in achieving live births among 644 infertile women with PCOS in China's Mainland.Methods and analysis:This is a prospective,randomized,multicentre,double-blinded,controlled design.Infertile women with PCOS were randomized into three-arm,letrozole and berberine,letrozole and berberine placebo,letrozole placebo and berberine.Data and blood were collected at baseline,the third month and sixth month after treatment,or immediately were collected if subject was pregnant.Statisticians and clinical investigators were blinded to treatment allocation and treatment related study results until the central database was locked for final data extraction and analysis determined.The statistical analysis plan described basic analysis principles,methods commonly encountered in data analysis issues,and the specific statistical procedures for analyzing the primary,secondary,and safety outcomes.Ethics and dissemination:The study was approved by the ethics committee of the First Affiliated Hospital,Heilongjiang University of Chinese Medicine.The study findings will be disseminated through peer-reviewed publications and conference presentations.Trial registration:Chinese Clinical Trial Registry:Chi CTR-TRC-09000376.Clinical Trials.gov identifier:NCT01116167.
